Fast multiparametric MR imaging as early biomarkers of Alzheimer's Disease

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Abstract Without a cure or prevention, Alzheimer's Disease (AD) rapidly will become an overwhelming economic and social burden. With the failure of multiple clinical trials targeting reduction of beta-amyloid (Aβ) burden and in general the stagnation of the development of effective treatment for AD, AD community believes that underlying causes of AD must be attacked before emergence of the cognitive phenotype. In this context, the development of predictive biomarkers and models is critical for identifying patients with high risk of rapid progression along the AD continuum, i.e. transitioning from normal cognition to mild cognitive impairment (MCI) and from MCI to dementia. Previous AD research has primarily been utilizing magnetic resonance imaging (MRI) for assessing morphological changes. Our preliminary results and other studies have shown that quantitative MR parameters such T1, T2, the magnetic susceptibility values are sensitive to normal ageing process and AD. However, their wide spread in AD research protocols has been limited due to scan time constraints. The overarching goal of the proposal is to establish a fast MR technique that does not increase overall scan time of a conventional MR protocol; and in addition to providing all the information the conventional protocol provides, it will also provide multiple quantitative parametric measurements specifically targeted to the needs of AD diagnosis and prognosis. We will 1) develop a fast and motion-insensitive MR technique (M3FAST-ECHO) that can generate multiple quantitative parameters within 10 minutes; 2) validate the volumetric measurement and microhemorrhage assessment from the synthetic 3D T1-weighted and the susceptibility weighted imaging from M3FAST-ECHO against standard ADNI protocol in 30 patients with mild cognitive impairment and 30 aged matched cognitively normal subjects; 3) compare quantitative T1, T2* and quantitative susceptibility values in 30 MCI patients and 30 aged matched cognitively normal subjects, and to correlate these metrics with neuropsychological measurements in the participants. The successful completion of the aims will result in a fast MR technique that provides multiple parametric MR maps without increasing overall scan time, and provide preliminary results for establishing values of quantitative MR parametric maps as sensitive biomarkers of AD. This will greatly enhance our ability to evaluate and screen for early predictive biomarkers of Alzheimer's Disease. The inter-disciplinary team and infrastructure for AD research at Emory will ensure successful execution of the study and dissemination of the developed techniques to the entire AD research community.